By investigating the role of prostaglandins (PG) in periodontal disease, we have found that gingival PGE2 levels are elevated in diseased periodontal tissue to the extent that the observed bone resorption could be the result of a continued presence of this agent. Experiments are now planned to initiate investigation of the role of PG in the development of periodontal disease in gnotobiotic rats infected with organisms isolated from human periodontal disease. The participation of PG in the disease mechanism will be tested by measuring gingival PG levels, excretion of urinary metabolites of PG and the effect of administrating drugs with Pg-synthetase inhibitor effects. This will be the first animal test of these drugs in the treatment of periodontal disease and may be used for initial animal testing should these drugs exhibit therapeutic value in these animal models. In addition, culture media supporting the growth of periodontal disease associated organisms will be tested for bone resorption activity to identify etiologic substances elaborated by the organisms. Drugs of the prostaglandin antagonist group will be further investigated for their abiliy to inhibit PG mediated bone resorption. The objective of these investigations is to determine the feasibility of treating certain forms of periodontal disease with drugs which interfere with the action of the prostaglandins and to test for causative chemical agents in cultures of periodontal disease organisms.